Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease

Michael D. Boska, Khader M. Hasan, Danette Kibuule, Rebecca Banerjee, Erin McIntyre, Jay A. Nelson, Theresa Hahn, Howard Eliot Gendelman, R Lee Mosley

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect > 50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p < 0.005) and decreased fractional anisotropy (p < 0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p ≤ 0.002) and correlated with the numbers of SN dopaminergic neurons (r = - 0.75, p = 0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

Original languageEnglish (US)
Pages (from-to)590-596
Number of pages7
JournalNeurobiology of Disease
Volume26
Issue number3
DOIs
StatePublished - Jun 1 2007

Fingerprint

Diffusion Tensor Imaging
Substantia Nigra
Parkinson Disease
Cerebral Ventricles
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Diffusion Magnetic Resonance Imaging
Corpus Callosum
Dopaminergic Neurons
Anisotropy
Tremor
Cerebral Cortex
Early Diagnosis
Biomarkers
Therapeutics

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Diffusion tensor imaging
  • Dopaminergic neurons
  • MPTP
  • Parkinson's disease
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology

Cite this

Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease. / Boska, Michael D.; Hasan, Khader M.; Kibuule, Danette; Banerjee, Rebecca; McIntyre, Erin; Nelson, Jay A.; Hahn, Theresa; Gendelman, Howard Eliot; Mosley, R Lee.

In: Neurobiology of Disease, Vol. 26, No. 3, 01.06.2007, p. 590-596.

Research output: Contribution to journalArticle

Boska, Michael D. ; Hasan, Khader M. ; Kibuule, Danette ; Banerjee, Rebecca ; McIntyre, Erin ; Nelson, Jay A. ; Hahn, Theresa ; Gendelman, Howard Eliot ; Mosley, R Lee. / Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease. In: Neurobiology of Disease. 2007 ; Vol. 26, No. 3. pp. 590-596.
@article{6681bb679be74a8b9bed935c0cc1f2b3,
title = "Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease",
abstract = "Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect > 50{\%} loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p < 0.005) and decreased fractional anisotropy (p < 0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p ≤ 0.002) and correlated with the numbers of SN dopaminergic neurons (r = - 0.75, p = 0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.",
keywords = "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Diffusion tensor imaging, Dopaminergic neurons, MPTP, Parkinson's disease, Striatum, Substantia nigra",
author = "Boska, {Michael D.} and Hasan, {Khader M.} and Danette Kibuule and Rebecca Banerjee and Erin McIntyre and Nelson, {Jay A.} and Theresa Hahn and Gendelman, {Howard Eliot} and Mosley, {R Lee}",
year = "2007",
month = "6",
day = "1",
doi = "10.1016/j.nbd.2007.02.010",
language = "English (US)",
volume = "26",
pages = "590--596",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease

AU - Boska, Michael D.

AU - Hasan, Khader M.

AU - Kibuule, Danette

AU - Banerjee, Rebecca

AU - McIntyre, Erin

AU - Nelson, Jay A.

AU - Hahn, Theresa

AU - Gendelman, Howard Eliot

AU - Mosley, R Lee

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect > 50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p < 0.005) and decreased fractional anisotropy (p < 0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p ≤ 0.002) and correlated with the numbers of SN dopaminergic neurons (r = - 0.75, p = 0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

AB - Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect > 50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p < 0.005) and decreased fractional anisotropy (p < 0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p ≤ 0.002) and correlated with the numbers of SN dopaminergic neurons (r = - 0.75, p = 0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

KW - Diffusion tensor imaging

KW - Dopaminergic neurons

KW - MPTP

KW - Parkinson's disease

KW - Striatum

KW - Substantia nigra

UR - http://www.scopus.com/inward/record.url?scp=34248582305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248582305&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2007.02.010

DO - 10.1016/j.nbd.2007.02.010

M3 - Article

C2 - 17428671

AN - SCOPUS:34248582305

VL - 26

SP - 590

EP - 596

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 3

ER -